PMID- 21317165 OWN - NLM STAT- MEDLINE DCOM- 20110516 LR - 20181201 IS - 1526-7598 (Electronic) IS - 0003-2999 (Linking) VI - 112 IP - 4 DP - 2011 Apr TI - A double-blind, randomized, multicenter study of MP4OX for treatment of perioperative hypotension in patients undergoing primary hip arthroplasty under spinal anesthesia. PG - 759-73 LID - 10.1213/ANE.0b013e31820c7b5f [doi] AB - BACKGROUND: MP4OX (oxygenated polyethylene glycol-modified hemoglobin) is a novel oxygen therapeutic agent specifically developed to perfuse and oxygenate tissue at risk for ischemia and hypoxia. In this study, we investigated the ability of MP4OX to treat hypotensive episodes. In addition, the tolerability profile of MP4OX in a large surgical population was established. METHODS: Patients from 21 study sites in 5 countries, scheduled to undergo primary hip arthroplasty under spinal anesthesia, were randomized in a double-blind manner to receive MP4OX or hydroxyethyl starch (HES) solution (Voluven(R); HES 130/0.4). Patients received the first 250-mL dose of investigational product when systolic blood pressure decreased to the predefined dosing trigger. A second 250-mL dose was given only if the systolic blood pressure decreased to the same trigger level after administration of the first dose. The primary efficacy outcome was total duration of all hypotensive episodes during surgery and the first 6 hours after skin closure. RESULTS: Of the 474 patients randomized, 405 reached the dosing trigger and received at least 1 dose. The mean total duration of all hypotensive episodes was significantly shorter (P < 0.0001) in the MP4OX group (52.4 +/- 71.50 minutes; range, 3-442 minutes) compared with the HES group (137.6 +/- 120.21 minutes; range, 5-435 minutes). The overall incidence of adverse events (AEs) in the intent-to-treat population was similar between the MP4OX and HES groups (75.2% vs 73.4%; P = 0.733). Transient increases in laboratory values were reported in more patients in the MP4OX group versus HES controls for aspartate aminotransferase (13.4% vs 7.4%; P = 0.052), alanine aminotransferase (6.9% vs 4.9%; P = 0.409), lipase (9.7% vs 3.6%; P = 0.015), and troponin (8.1% vs 2.0%; P = 0.006). There was no significant difference in the incidence of serious AEs reported (6.4% in MP4OX group vs 3.0% in HES controls; P = 0.106). Certain AEs did occur more frequently in the MP4OX group, including nausea (23.8% vs 14.3%; P = 0.016), bradycardia (14.9% vs 5.9%; P = 0.003), hypertension (8.4% vs 2.5%; P = 0.009), and oliguria (5.9% vs 1.5%; P = 0.019). The composite morbidity and ischemia end points did not reveal any differences between the 2 treatment groups. CONCLUSIONS: Administration of MP4OX achieved the end point of treating perioperative hypotension in patients undergoing primary hip arthroplasty under spinal anesthesia. The study was not powered to demonstrate clinical benefit based on the composite morbidity or ischemia outcomes. Although efficacy end points with sufficient power were met, MP4OX is not being proposed for use in routine surgery where the risk-benefit profile would not be favorable based on the safety profile demonstrated in this study. FAU - van der Linden, Philippe AU - van der Linden P AD - Department of Anesthesiology, CHU Brugmann, Brussels, Belgium. FAU - Gazdzik, Tadeusz S AU - Gazdzik TS FAU - Jahoda, David AU - Jahoda D FAU - Heylen, Rene J AU - Heylen RJ FAU - Skowronski, Jan C AU - Skowronski JC FAU - Pellar, David AU - Pellar D FAU - Kofranek, Ivo AU - Kofranek I FAU - Gorecki, Andrzej Z AU - Gorecki AZ FAU - Fagrell, Bengt AU - Fagrell B FAU - Keipert, Peter E AU - Keipert PE FAU - Hardiman, Yun J AU - Hardiman YJ FAU - Levy, Howard AU - Levy H CN - 6090 Study Investigators LA - eng PT - Comparative Study PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20110211 PL - United States TA - Anesth Analg JT - Anesthesia and analgesia JID - 1310650 RN - 0 (Hemoglobins) RN - 3WJQ0SDW1A (Polyethylene Glycols) RN - S88TT14065 (Oxygen) SB - IM MH - Aged MH - Aged, 80 and over MH - *Anesthesia, Spinal/adverse effects MH - *Arthroplasty, Replacement, Hip/adverse effects MH - Double-Blind Method MH - Female MH - Hemoglobins/*administration & dosage MH - Humans MH - Hypotension/*drug therapy/etiology/physiopathology MH - Internationality MH - Male MH - Middle Aged MH - Oxygen/*administration & dosage MH - Perioperative Care/methods MH - Polyethylene Glycols/*administration & dosage MH - Treatment Outcome FIR - van der Linden, Philippe IR - van der Linden P FIR - Dierick, Ann IR - Dierick A FIR - Putz, Philippe IR - Putz P FIR - Sessego, Bruna IR - Sessego B FIR - Heylen, Rene J IR - Heylen RJ FIR - van Poucke, Sven IR - van Poucke S FIR - Hens, Ria IR - Hens R FIR - Debucquoy, Philippe IR - Debucquoy P FIR - Decoster, Olivier IR - Decoster O FIR - Van den Daelen, L IR - Van den Daelen L FIR - Demets, Lieven IR - Demets L FIR - Zmolik, Ludek IR - Zmolik L FIR - Lepsi, Zdenka IR - Lepsi Z FIR - Teyssler, Petr IR - Teyssler P FIR - Jahoda, David IR - Jahoda D FIR - Vcela, Lubos IR - Vcela L FIR - Tomaides, Jan IR - Tomaides J FIR - Pokomy, David IR - Pokomy D FIR - Hromadka, Rastislav IR - Hromadka R FIR - Sosna, Antonin IR - Sosna A FIR - Hykesova, Alena IR - Hykesova A FIR - Pellar, David IR - Pellar D FIR - Dolezal, David IR - Dolezal D FIR - Karpas IR - Karpas FIR - Winklerova, Magdalena IR - Winklerova M FIR - Kofranek, Ivo IR - Kofranek I FIR - Hajny, Petr IR - Hajny P FIR - Konopasek IR - Konopasek FIR - Kubes IR - Kubes FIR - Kafunek, Martin IR - Kafunek M FIR - Kompelentova, Lucie IR - Kompelentova L FIR - Stastna, Ivana IR - Stastna I FIR - Gommers, Diederik IR - Gommers D FIR - Moors IR - Moors FIR - Verhaar, J A IR - Verhaar JA FIR - Roubos, Steven IR - Roubos S FIR - van der Vis, Harm M IR - van der Vis HM FIR - Taminiau, Lucas IR - Taminiau L FIR - Heerlien, Laura IR - Heerlien L FIR - Groen, Floris Reinder IR - Groen FR FIR - Verheijen, Raymond IR - Verheijen R FIR - Simon, Mark IR - Simon M FIR - Setz IR - Setz FIR - Dirksen, Ris IR - Dirksen R FIR - Gort, C IR - Gort C FIR - Bergshoeff, Ineke IR - Bergshoeff I FIR - Luijkx, Florent IR - Luijkx F FIR - Maldyk, Pawel IR - Maldyk P FIR - Michalak, Cezary IR - Michalak C FIR - Lisowska, Barbara IR - Lisowska B FIR - Slowinska, Iwona IR - Slowinska I FIR - Sakrajda, Elzbieta IR - Sakrajda E FIR - Gazdzik, Tadeusz IR - Gazdzik T FIR - Bozek, Marek IR - Bozek M FIR - Bielecki, Tomasz IR - Bielecki T FIR - Kuk, Alberski Ewa IR - Kuk AE FIR - Skowronski, Jan C IR - Skowronski JC FIR - Dlugosz, Jerzy IR - Dlugosz J FIR - Karpik, Marta IR - Karpik M FIR - Dolzynski, Maciej IR - Dolzynski M FIR - Gorecki, Andrzej Z IR - Gorecki AZ FIR - Nowakowski, Piotr IR - Nowakowski P FIR - Skowronek, Pawel IR - Skowronek P FIR - Gorski, Radoslaw IR - Gorski R FIR - Olszewski, Pawel IR - Olszewski P FIR - Majewski, Jacek IR - Majewski J FIR - Szczygiel, Rafal IR - Szczygiel R FIR - Hermanson, Jacek IR - Hermanson J FIR - Pajak IR - Pajak FIR - Sandin, Rolf IR - Sandin R FIR - Glatz, Pia IR - Glatz P FIR - Ahlstrom, Martin IR - Ahlstrom M FIR - Lindholm, Maj-Lis IR - Lindholm ML FIR - Frankzen, Mats IR - Frankzen M FIR - Antonsson, Margareta IR - Antonsson M FIR - Ahl, Torbjorn IR - Ahl T FIR - Fredriksson, Inga IR - Fredriksson I FIR - Bjurman, Birgitta IR - Bjurman B FIR - Andersson, Camilla IR - Andersson C FIR - Ponzer, Sari IR - Ponzer S FIR - Svensen, Christer IR - Svensen C FIR - Lapidus, Lasse IR - Lapidus L FIR - Levander, Catherina IR - Levander C FIR - Skogman, Elizabeth IR - Skogman E FIR - Johansson, Torsten IR - Johansson T FIR - Horn, Bengt IR - Horn B FIR - Ledin, Hakan IR - Ledin H FIR - Henriksson, Carmen IR - Henriksson C FIR - Ledin-Eriksson, Susanne IR - Ledin-Eriksson S FIR - Kargsten, Georg IR - Kargsten G FIR - Sundgren, Kent IR - Sundgren K FIR - Knudsen, Kati IR - Knudsen K FIR - Lidberg, Tanja IR - Lidberg T FIR - Dolonius, Leif IR - Dolonius L FIR - Hessel, Monica IR - Hessel M FIR - Rorqvist, Rose-Marie IR - Rorqvist RM EDAT- 2011/02/15 06:00 MHDA- 2011/05/17 06:00 CRDT- 2011/02/15 06:00 PHST- 2011/02/15 06:00 [entrez] PHST- 2011/02/15 06:00 [pubmed] PHST- 2011/05/17 06:00 [medline] AID - ANE.0b013e31820c7b5f [pii] AID - 10.1213/ANE.0b013e31820c7b5f [doi] PST - ppublish SO - Anesth Analg. 2011 Apr;112(4):759-73. doi: 10.1213/ANE.0b013e31820c7b5f. Epub 2011 Feb 11.